The investigations proposed herein embrace three aspects of the role of oxygen as the common denominator linking clinical hematology to pulmonary and cardiovascular medicine. (1) Evidence exists to suggest that certain physiologic responses manifested by humans upon exposure to altitude are, in fact, maladaptive. This concept will be examined through the working hypothesis that humans with high oxygen affinity hemoglobins are pre-adapted to altitude exposure. (2) Recent investigations have indicated that granulocytes stimulated in vivo by activated complement are of major pathogenetic significance in the development of a variety of human diseases involving the pulmonary-vascular endothelium. The mechanisms of this apparent granulocyte/endothelial interaction will be evaluated in an endothelial cell culture system. It is hypothesized that free radicals are an integral feature of this recently observed pathogenetic axis. (3) Platelets have long been known to be associated (morphologically) with injured vascular endothelium. The causality of this association is less certain. These investigations will address this by identifying apparent mechanisms of platelet/endothelial interaction, again utilizing an endothelial cell culture system. In addition, a previously unknown phenomenon of platelet responsiveness (chlorine-induced aggregation) has been observed. Preliminary evidence indicates that this observation is of importance to our understanding of the role of oxidants and free radical in platelet function and physiology. It is hypothesized that these toxic species are of possible etiologic importance in the pathogenesis of vascular endothelial disease, the prototype of which is atherosclerosis. As a possible model for the role of free radicals in platelet-mediated disease, the mechanism and significance of chlorine-induced platelet aggregation will be defined.